Liquid formulations of urease inhibitors for fertilizers

ABSTRACT

An improved solvent system for the formulation and application of N-alkyl thiophosphoric triamide urease inhibitors. These formulations provide safety and performance benefits relative to existing alternatives and enable storage, transport and subsequent coating or blending with urea based or organic based fertilizers. These formulations are comprised primarily of environmentally friendly aprotic and protic solvents (particularly dimethyl sulfoxide and alcohols/polyols) to stabilize the urease inhibitor.

The present application is a continuation and claims priority under 35 §USC 120 to U.S. application Ser. No. 15/636,211 filed Jun. 28, 2017,which in turn is a continuation and claims priority to U.S. applicationSer. No. 13/890,082 filed May 8, 2013, which in turn claims priorityunder 35 § USC 119(e) to U.S. Provisional Application 61/708,105 filedOct. 1, 2012, the entire contents of all of which are herebyincorporated by reference in their entireties.

FIELD OF THE INVENTION

In embodiments, the present invention relates to improved solventformulations for the urease inhibitor N-(n-butyl) thiophosphorictriamide, hereafter referred to by its acronym NBPT. NBPT is a solidchemical substance, which is dissolved in a suitable solvent to allowapplication at low levels in the field. Additionally, solutions of NBPTare desirable when it is to be incorporated as a component of a granularmixed fertilizer, such that it can be deposited as a coating in acontrolled and homogenous layer. In one embodiment, this inventionproposes formulations of mixtures containing aprotic and protic solventswhich are more environmentally friendly and are safer for workers tohandle than known NBPT solutions. Moreover, performance advantagesrelative to NBPT solution stability, solution handling, and loadinglevels are disclosed for these new formulations.

BACKGROUND OF THE INVENTION Description of the Prior Art

Nitrogen is an essential plant nutrient and is thought to be importantfor the adequate and strong foliage. Urea provides a large nitrogencontent and is one of the best of all nitrogenous fertilizer materials,which consequently makes it an efficient fertilizer compound. In thepresence of soil moisture, natural or synthetic ureas are converted toammonium ion, which is then available for plant uptake. When applied asa fertilizer material, native soil bacteria enzymatically convert ureato two molar equivalents of ammonium ion for each mole of urea asdemonstrated by the following two reactions:CO(NH₂)₂+2H₂O→(NH₄)₂CO₃(NH₄)₂CO₃+2H⁺→2NH₄ ⁺+CO₂+H₂O

In the presence of water, the ammonium thus produced is in equilibriumwith ammonia. The equilibrium between NH₄ ⁺ and NH₃ is pH dependent, inaccordance with the following equilibrium:NH₄ ⁺+OH⁻↔NH_(3(solution))+H₂O

As such, gaseous ammonia losses are higher at higher pH values. The fluxof NH₃ from soil is primarily dependent on the NH₃ concentration, pH,and temperature. In the presence of oxygen, ammonium can also beconverted to nitrate (NO₃ ⁻). Nitrogen in both its ammonium and nitrateforms may then be taken up as nutrient substances by growing plants.

The ammonium ion can also ultimately be converted to ammonia gas, whichescapes to the air. The concentrations of NH₃ in the air and in solutionare governed by Henry's law constant (H), which is a function oftemperature:└NH_(3(air))┘=H└NH_(3 (solution))┘

Urea fertilizer is often just applied once at the beginning of thegrowing season. A weakness in this nitrogen delivery system involves thedifferent rates at which ammonium and nitrate are produced in the soil,and the rate at which ammonium and nitrate are required by the plantduring its growing season. The generation of ammonium and nitrate isfast relative to its uptake by plants, allowing a considerable amount ofthe fertilizer nitrogen to go unutilized or to be lost to the atmosphereas ammonia gas, where it is no longer available to the plant. Thus,there is a desire to control the hydrolysis of urea to ammonium andammonia gas, thereby making the urea fertilizer more effective for plantgrowth.

Numerous methods have been developed for making urea fertilizers moreeffective, and for controlling the volatilization of ammonia from urea.Weston et al. (U.S. Pat. No. 5,352,265) details a method for controllingurea fertilizer losses, including: (1) multiple fertilizer treatments inthe field, staged across the growing season, (2) the development of‘controlled release’ granular fertilizer products, using protectivecoatings which erode slowly to introduce the urea to the soil in acontrolled fashion, and (3) the discovery of simple chemical compounds(urease inhibitors) which inhibit the rate at which urea is metabolizedby soil bacteria and converted to the ammonium ion.

Use of various urea coatings to provide urea in a controlled fashion tothe plant has been widely demonstrated. Phosphate coatings for urea havebeen described by Barry et al. (U.S. Pat. No. 3,425,819) wherein thecoating is applied to urea as an aqueous phosphate mixture. Miller (U.S.Pat. No. 3,961,932) describes the use of chelated micronutrients to coatfertilizer materials. Polymer coatings have also been disclosed whichcontrol the delivery of fertilizer materials (see, for example, U.S.Pat. Nos. 6,262,183 and 5,435,821).

Whitehurst et al. (U.S. Pat. No. 6,830,603) teach the use of boratesalts to produce coated urea fertilizer, as a means of controllingammonia losses during the growth cycle. Whitehurst summarizes numerousexamples of this coating strategy to inhibit the loss of ammonianitrogen in the soil. Accordingly, the prior art considers the merits ofcoated fertilizer products as one means of inhibiting the loss ofammonia nitrogen in the soil. Urease inhibiting materials other thanNBPT have been disclosed. Some examples include the use of polysulfideand thiosulfate salts as taught by Hojjatie et al (US 2006/0185411 A1)and the use of dicyandiamide (DCD) and nitrapyrin.

Kolc at al. (U.S. Pat. No. 4,530,714) teach the use of aliphaticphosphoric triamide urease inhibitors, including the use of NBPT forthis purpose. Kolc mentions the use of aqueous and organic carriermedia, but specifies volatile (and flammable) solvents from the groupincluding acetone, diisobutylketone, methanol, ethanol, diethyl ether,toluene, methylene chloride, chlorobenzene, and petroleum distillates.The principle reason for the use of these solvents was to assure thatnegligible amounts of solvent residue be retained on the crop.

Improved carrier systems for NBPT have been described subsequent to theKolc. NBPT is both a hydrolytically and thermally unstable substance andseveral solvent systems have been developed to overcome these and otherweaknesses. Unfortunately, the existing formulations are problematic intheir own right due to thermal stability concerns and the toxicity ofkey formulation components.

Generally, it is desirable that solvents being used in conjunction withfertilizers be water soluble in all proportions which allows for faciledispersion at the point of use as well as a relatively high flashpoint(so that it has a reduced chances of explosions and/or fires at elevatedtemperatures). Many of the formulation solvents disclosed in U.S. Pat.No. 4,530,714 do not possess these desirable properties. Examples ofsuch problematic solvents from this patent include the use of toluene, aflammable and water immiscible solvent.

Weston et al. (U.S. Pat. No. 5,352,265) disclose the use of pyrrolidonesolvents, such as N-Methyl pyrrolidone (NMP), as does Narayanan et al.(U.S. Pat. Nos. 5,160,528 and 5,071,463). It is shown that a solvents ofthis type can dissolve high levels of NBPT to produce productconcentrates and that the resulting concentrates have good temperaturestability. These features are useful in that they allow commercialproducts to be stored, pumped, and transported in conventional ways.

In U.S. Pat. No. 5,698,003, Omilinsky and coworkers also disclose theuse of ‘liquid amides” such as NMP in NBPT formulations. Omilinskyfurther speaks to the importance of solution stability and developsglycol-type solvents as desirable base solvents for NBPT deliverymixtures. The dominant role played by a liquid amide co-solvent is todepress the pour point of the mixture, which is insufficiently high as aconsequence of the natural viscosity of glycols at reduced temperatures.NMP plays several roles in NBPT-based agrichemical formulations. Astaught in '265, '528, and '463, NMP is a useful solvent capable ofproducing concentrated NBPT product formulations which have goodtemperature stability. It may also be used as an additive to depress thepour point of viscous base solvents, such as propylene glycol. Omilinskydiscloses the use of NMP as a co-solvent to depress the pour point ofpropylene glycol in '003.

In mixtures such as those described in U.S. Pat. No. 5,698,003, therequirement for an additive to depress the pour point of glycol-typeNBPT solvent formulations is described. Solvents such as propyleneglycol have the attractive feature of being essentially nontoxic and arethus an attractive mixture component in agrichemical and pharmaceuticalproducts. One drawback of some glycols is a relatively high viscositylevel, which can make these materials resistant to flow and difficult topour. Indeed, the dynamic viscosity at 25° C. of propylene glycol is48.8 centipoise, almost 50 times that of water at the same temperature.Viscosity data for propylene glycol can be found in Glycols (Curme andJohnston, Reinhold Publishing Corp., New York, 1952). Omilinsky '003describes the use of NMP as an additive capable of depressing the pourpoint of NBPT mixtures.

Although NMP and other liquid amide solvents play useful roles in thedescribed NBPT formulations, concerns about the safety of these solventshas increased greatly in recent years. In particular, EuropeanDirectives 67/548/EEC and/or 99/45/EC have recently classifiedN-methylpyrrolidone (NMP) as a reproductive toxin (R61) in amountsexceeding 5% of the product formulation. It is scheduled for listing onthe European Union's ‘Solvent of Very High Concern’ list, which wouldpreclude its use in industrial and agrichemical formulations. In the US,NMP is subject to California Proposition 65 (The Safe Drinking Water andToxic Enforcement Act of 1986) requirements, which regulate substancesknown by the US State of California to cause cancer or reproductiveharm.

Nothing in the prior art addresses the suitability of NMP in theseformulations from the standpoint of safety, or proposes appropriatealternatives from the perspectives of both safety and performance.

Indeed, guidelines for the use of reaction solvents in thepharmaceutical industry also speak to the relatively poor safety profileof NMP. As reaction solvents may be present at residual levels infinished drug products such considerations are warranted. TheInternational Conference on Harmonization of Technical Requirements forRegistration of Pharmaceuticals for Human Use (ICH) classifies NMP as a‘solvent to be limited (Class 2)’ in its document Impurities: Guidelinefor Residual Solvents Q3C (R3).

NMP is potentially toxic if it is given directly to humans and/oranimals. Moreover, it is possible that NMP may be toxic when it isingested by higher order animals after passage through the food chain.For example, often times, fertilizers are not completely absorbed/usedby fields/crops/plants on which they are used and the fertilizers end upin water-ways (such as fresh water, brackish water or salt waterbodies). In those situations where at least a part of the fertilizerends up in these bodies of water, they may be absorbed, ingested orotherwise taken in by organisms that are either directly or indirectlyconsumed by higher animals (such as humans). In these instances, it ispossible that the fertilizer and/or compounds that are associated withsaid fertilizer may be directly and/or indirectly ingested by humans orhigher animals and lead to toxicity to said humans. It is also possiblethat the fertilizers that end up in water ways may be directly ingestedby higher animals/humans that drink the water.

Moreover, when toxic compounds that are associated with variousfertilizers are used, not only may they be toxic to the higher animalsbut they also may be toxic to the animals lower in the food chain. Athigher doses, this may mean die-off of the animals lower in the foodchain, which consequently means that there may be economic consequencessuch as crop and/or animal die-off, which means lower profit margins andless food available.

In light of the above, it is desirable to developformulations/fertilizers that are less toxic to the environment and toanimals and humans.

An important feature of NBPT-based agrichemical formulation is theirchemical stability in solution. Although such products are diluted withwater at the point of use, NBPT undergoes hydrolysis in the presence ofwater. Aqueous solutions or emulsions of NBPT are therefore notpractical from a commercial perspective and organic solvents arepreferred as vehicles to deliver concentrated NBPT products. But NBPT isnot chemically inert to all solvents, and its stability must be assessedin order to develop a product suitable to the needs of agrichemicalusers.

The stability of NBPT to NMP has been previously established in U.S.Pat. No. 5,352,265 (Weston et al.) and by Narayanan et al. (U.S. Pat.Nos. 5,160,528 and 5,071,463).

Beyond the consideration of NBPT chemical stability in the presence offormulation solvents is the inherent stability of the solventsthemselves to hydrolysis. As NBPT products are often ultimatelydispersed into water, the hydrolytic stability of liquid amide solventslike NMP is a consideration.

At elevated temperatures and pH levels, NMP hydrolysis can besignificant (“M-Pyrrol” product bulletin, International SpecialtyProducts, p. 48).

SUMMARY OF THE INVENTION

In one embodiment, the present invention relates to liquid formulationscontaining N-(n-butyl) thiophosphoric triamide (NBPT). In an embodiment,the formulations can be made by dissolving the NBPT into an aproticsolvent consisting of a) dimethyl sulfoxide, b) dialkyl, diaryl, oralkylaryl sulfoxide having the formula R₁—SO—R₂, when R₁ is methyl,ethyl, n-propyl, phenyl or benzyl and R₂ is ethyl, n-propyl, phenyl orbenzyl, c) sulfolane, d) ethylene carbonate, propylene carbonate, ormixtures thereof. In an embodiment, these formulations can be mixed witha protic component consisting of 1) an alcohol or polyol from the familyof alkylene and poly(alkylene) glycols (PG), 2) an alkylene glycol fromthe group comprised of ethylene, propylene, or butylene glycol, 3)glycerin, 4) an alkanolamine from the group comprising ethanolamine,diethanolamine, dipropanolamine, methyl diethanolamine,monoisopropanolamine and triethanolamine, and/or 5) ethyl, propyl, orbutyl lactate. In one embodiment, we propose the use of dimethylsulfoxide (DMSO) as a replacement in NBPT-based agrichemical productsfor more toxic solvents such as, for N-methyl pyrrolidone.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 shows accelerated chemical stability of NBPT solutions comparingthe test product (50% PG, 25% DMSO, 25% NBPT) vs. the commercial productcontaining N-methyl pyrrolidone. The stability testing was conducted at50° C., and concentrations were assayed by HPLC.

FIG. 2 shows accelerated chemical stability of NBPT solutions comparingthe test product (35% PG, 40% DMSO, 25% NBPT) vs. the commercial productcontaining N-methyl pyrrolidone. The stability testing was conducted at50° C., and concentrations were assayed by HPLC.

FIG. 3 shows accelerated chemical stability of NBPT solutions comparingthe test product (20% PG, 40% DMSO, 40% NBPT) vs. the commercial productcontaining N-methyl pyrrolidone. The stability testing was conducted at50° C., and concentrations were assayed by HPLC.

FIG. 4 shows accelerated chemical stability of NBPT solutions comparingthe test product (48.5% glycerine, 1.5% methanol, 25% DMSO, 25% NBPT)vs. the commercial product containing N-methyl pyrrolidone. Thestability testing was conducted at 50° C., and concentrations wereassayed by

FIG. 5 shows accelerated chemical stability of NBPT solutions comparingthe test product (48.5% glycerine, 1.5% methanol, 25% DMSO, 25% NBPT)vs. the commercial product containing N-methyl pyrrolidone. Thestability testing was conducted at 50° C., and concentrations wereassayed by HPLC.

FIG. 6 shows accelerated chemical stability of four NBPT solutions: MixA; 75.0% N-methyl pyrrolidone, 25% NBPT. Mix B; 75 PG, 25% NBPT. Mix C;75.0% Buffered mix, 25.0% NBPT. Mix D; 75% DMSO, 25.0% NBPT. Thestability testing was conducted at 50° C., and concentrations wereassayed by HPLC.

FIG. 7 shows viscosity testing results comparing mixtures of propyleneglycol with varying percentages of co-solvents DMSO vs. NMP. Viscositieswere measured using a Brookfield LVDV-E digital rotational viscometerwith LVDV-E spindle set. Also shown is the viscosity of the commercialNBPT product, which contains NMP and PG, of example 2.

FIG. 8 shows viscosity testing results comparing mixtures of glycerolwith varying percentages of co-solvents DMSO vs. NMP. Viscosities weremeasured using a Brookfield LVDV-E digital rotational viscometer withLVDV-E spindle set. Also shown is the viscosity of the commercial NBPTproduct, which contains NMP and PG, of example 2.

FIG. 9 shows viscosity testing results comparing mixtures ofmonoisopropanolamine (MIPA) with varying percentages of co-solvents DMSOvs. NMP. Viscosities were measured using a Brookfield LVDV-E digitalrotational viscometer with LVDV-E spindle set. Also shown is theviscosity of the commercial NBPT product, which contains NMP and PG, ofexample 2.

FIG. 10 shows ammonia emissions testing results from soil which had beenapplied commercial urea fertilizer vs. commercial urea fertilizer coatedwith an NBPT solution containing 50.0% PG, 30.0% DMSO, and 20.0% NBPT byweight. The testing was conducted for 7 days at 22° C. using acommercially available potting soil blend, and was analyzed using achemiluminescence ammonia analyzer.

DETAILED DESCRIPTION OF THE INVENTION

In an embodiment, the present invention relates to formulationscontaining N-(n-butyl) thiophosphoric triamide (NBPT). In an embodiment,these formulations are prepared by dissolving NBPT into an aproticsolvent consisting of a) dimethyl sulfoxide, b) dialkyl, diaryl, oralkylaryl sulfoxide having the formula R₁—SO—R₂, when R₁ is methyl,ethyl, n-propyl, phenyl or benzyl and R₂ is ethyl, n-propyl, phenyl orbenzyl, c) sulfolane, d) ethylene carbonate, propylene carbonate, ormixtures thereof. In an embodiment, these formulations can be mixed witha protic component consisting of 1) an alcohol or polyol from the familyof alkylene and poly(alkylene) glycols (PG), 2) an alkylene glycol fromthe group comprised of ethylene, propylene, or butylene glycol, 3)glycerin, 4) an alkanolamine from the group comprising ethanolamine,diethanolamine, dipropanolamine, methyl diethanolamine,monoisopropanolamine and triethanolamine, and/or 5) ethyl, propyl, orbutyl lactate.

In one embodiment, dimethyl sulfoxide (DMSO) is used as a replacement inNBPT-based agrichemical products for more toxic solvents such as, forN-methyl pyrrolidone (NMP).

In one embodiment, the solution is either combined with a dry granularor liquid urea fertilizer and applied to cropland to make the fertilizermore effective for plant growth, and/or applied directly tourea-containing lands, surfaces, or products to reduce ammoniaemissions.

In one embodiment, coated granular urea products containing additionalplant nutrients can be prepared from granular urea, a source or sourcesof the additional nutrients in powdered form and the diluted NBPTcontaining mixture described below. Granular urea can be first dampenedwith the diluted NBPT containing mixture followed by mixing todistribute the NBPT containing liquid mixture over the granular ureasurface using any commonly used equipment to commingle a liquid with agranular solid. After distribution of the diluted NBPT containingmixture over the granular surface, the additional nutrients in powderedform can be added to the dampened mixture and the resulting combinedingredients can be further mixed to distribute the powdered materials.In an alternate embodiment, the powdered materials may be first mixedwith the granular urea and then the NBPT containing diluted mixture canbe sprayed onto a tumbling bed of the dry ingredients to agglomerate thedry materials. This latter method may be particularly suited tocontinuous processing.

The term “urea fertilizer” as used herein refers to both natural andsynthetic ureas, either used alone or mixed with other macro- and/ormicronutrients and/or organic matter. Dry granular urea fertilizercontains about 46% nitrogen by weight.

In one embodiment, the compounds listed in this invention as aprotic andprotic solvents may be described generally as sulfoxides and alcohols,respectively.

In an embodiment, the present invention relates to the use of safer andmore environmentally friendly solvents to overcome the limitations ofspecific existing urease inhibitor formations. In an embodiment, thesolvents used in the present invention are less toxic than the solventsthat have been used in the prior art, for example, NMP.

In an embodiment, the formulations use combinations of polar aproticsolvents (sulfoxides, sulfones, dialkyl carbonates) with protic solvents(glycols, triols, and alkanolamines) to produce NBPT formulations havingacceptable viscosity levels and high NBPT loading while also beingrelatively non-toxic. Moreover, in an embodiment, the protic/aproticsolvent mixtures demonstrate excellent NBPT stability as demonstrated byaccelerated stability testing.

One aspect of the invention involves the use of dimethyl sulfoxide as areplacement for the more hazardous liquid amide component informulations requiring such a co-solvent to modify the formulation'sflow properties. In this aspect, this is a considerable improvement inlight of increased regulatory scrutiny of the liquid amide solvents.

In one embodiment, the present invention relates to the use of DMSO withNBPT instead of NMP. NMP has a recognized reproductive toxicity and anexamination of acute toxicity data shows that NMP is considerably morehazardous than dimethyl sulfoxide, by any exposure route. A summary ofbasic toxicological indicators is given in Table 1.

TABLE 1 Comparative acute/reproductive toxicity data for dimethylsulfoxide and N-methyl pyrrolidone. Toxicological Dimethyl sulfoxideN-methyl pyrrolidone indicator CAS [67-68-4] [872-50-4] Oral LD-5014,500-28,300 3,914 Dermal LD-50 40,000 8,000 Inhalation Noneestablished 3200 μg/day toxicity (MADL) Reproductive toxin no yes MADL =Maximum Allowable Dosage Level per day (California Proposition 65)

As shown in the table above, it should be clear to those of ordinaryskill in the art that DMSO is significantly less toxic than NMP.Furthermore, DMSO is classified as ‘a solvent with low toxic potential(Class 3)’—the most favorable rating.

In one embodiment, the present invention addresses the shortcomings ofsolvents of the prior art by the use of specific mixtures of lowtoxicity polar aprotic solvents (most principally dimethyl sulfoxide)and various common protic solvents, that also tend to be relativelynon-toxic.

In an embodiment, the present invention relates to formulationscomprising aprotic/protic solvent mixtures that are used to fluidize thespecific urease inhibitor N-(n-butyl) thiophosphoric triamide such thatit might be used to coat fertilizer products.

In one embodiment, phosphate coatings for urea may be used wherein thecoating is applied to urea as an aqueous phosphate mixture prior toadding the fertilizer additive of the present invention.

In an embodiment, chelated micronutrients may be used to coat fertilizermaterials. Alternatively and/or additionally, polymer coatings may beused which control the delivery of fertilizer materials.

In one embodiment, the formulations of the present invention use DMSO asa solvent. DMSO has an advantage over prior art solvents such as NMPbecause DMSO does not undergo the hydrolysis that can be significantwith NMP (see “M-Pyrrol” product bulletin, International SpecialtyProducts, p. 48). Accordingly, when one uses DMSO, one has significantlymore latitude in formulation development.

Further, the solvent properties of DMSO are useful in these formulationsin that NBPT concentrations containing over 50 wt. % NBPT areattainable. Such high loading of an active substance by a solventenables the manufacture of product concentrates, which can be lessexpensive to store, transport and use. When the fertilizer additiveproduct arrives at the user, the user is able to dilute the concentratewith water and use the fertilizer additive (with fertilizer) for theircrops/plants or the like.

In one embodiment, NBPT is dissolved into an aprotic solvent such asdimethyl sulfoxide. The NBPT-aprotic solvent solution may be used alone,or further mixed with a protic solvent to improve product handling,stability, and/or pourability of the solution.

The mixing of the materials may be accomplished in any commonly usedmethod: for example; simply tank mixing materials prior to use, using ametering system to inject materials simultaneously, or mixing via aspray injection system.

In one embodiment, the NBPT/aprotic solvent/protic solvent mixture ismixed to produce a NBPT concentration of 5% to 75% by weight.Alternatively, a NBPT concentration of 5% to 60% by weight may be used.Alternatively, a NBPT concentration of 5% to 50% by weight may be used.Alternatively, a NBPT concentration of 5% to 40% by weight may be used.The initial solubilizing step in dimethyl sulfoxide can be accomplishedbetween room temperature about 19° C. up to about 150° C. (the boilingpoint of DMSO at atmospheric pressure is ˜190° C.). Alternatively, thesolubilizing step in dimethyl sulfoxide can be accomplished betweenabout 22° C. and up to 60° C.

The mixture can be mixed in any common mixing tank. Although themetering of NBPT, aprotic solvent, and protic solvent can be based on aweight, it may also be based on a volumetric basis.

A dye or colorant can be added to the mixture to aid in visualassessment of uniform coating during the coating of granular urea.Alternatively, a dye or colorant can be added to the mixture to aid invisual assessment of uniform coating during the coating of urea inaqueous mixtures just prior to application. In one embodiment, thecolorant can include any nontoxic common food dye.

EXAMPLES

The following examples are provided to illustrate the practice of theinvention. The examples are not intended to illustrate the completerange of possible uses. All compositions are based on mass percentagesunless expressly stated. Concentrations of individual components arepresented before their name. For example, 20.0% NBPT refers to a mixturecontaining 20.0% NBPT by weight.

Example 1

An NBPT solution was prepared by thoroughly mixing NBPT, DMSO, and PG toobtain the following percentages by weight: 50.0% PG, 30.0% DMSO, 20.0%NBPT.

Example 2

To test for the toxicity of DMSO and compare it to the relative toxicityof NMP, a 96 hr. acute toxicity range-finding test was conducted onjuvenile crayfish (Procambarus clarkii) to estimate the lethalconcentration to half of the population (LC₅₀) for the solution asdescribed in example 1. Simultaneously, the LC₅₀ was determined on acommercially available NBPT solution which contained 26.7% NBPT byweight (per product label), and approximately 10% N-methyl pyrrolidone(MSDS range 10-30%), and approximately 63% propylene glycol (MSDS range40-70%). Crayfish were placed into static chambers and exposed to equalNBPT concentrations of 0, 72, 145, 290, 580, and 1160 mg/L in cleanwater. The LC₅₀ of the solution of example 1 was 145 mg NBPT (as activeingredient)/L, while the LC₅₀ of Agrotain® Ultra was 75 mg NBPT (asactive ingredient)/L. Because a higher LC₅₀ value indicates lowertoxicity, the solution of example 1 was approximately half as toxic asthe commercial product which contained N-methyl pyrrolidone.

This test demonstrates that the formulations of the present inventionare significantly less toxic than the formulations of the prior art.

Example 3

NBPT solutions were prepared in DMSO and equal amounts of DMSO/PG todetermine the maximum solubility at room temperature of 22° C. Followingmixing and sonification, the samples were visually inspected, thenfiltered through a 0.45 μm filter and analyzed by near infraredreflectance spectrometry. At 22° C., the solubility of NBPT in DMSO wasat least 58.9% by weight. The solubility of NBPT in equal amounts ofDMSO/PG was at least 55.0% by weight.

It would be expected that at increased temperatures beyond thatdisclosed above, one might be able to increase the solubility of NBPTabove the amounts found in this example providing an avenue forconcentrates. Even if the temperature is lowered during transport,instructions on the use of the fertilizer additive may instruct the userto raise the temperature of the formulation to assure completesolubilization of the product prior to use.

Example 4

An NBPT solution was prepared by thoroughly mixing NBPT, DMSO, and PG toobtain the following percentages by weight: 50% PG, 25% DMSO, and 25%NBPT. The commercially available NBPT solution of example 2 was alsoused for comparison.

Example 5

The NBPT solutions of example 4 were placed into individual vials andincubated for 45 days at 50±1° C. in a laboratory oven. Samples wereperiodically removed for analysis of NBPT in solution using a Watersmodel 1525 High Performance Liquid Chromatograph (HPLC) equipped with aWaters 2489 tunable UV/visible detector. Suitable analytical parameters(mobile phase composition, column selection, etc.) such as would occurto workers knowledgeable in the art were employed, and raw data from theHPLC analyses were calibrated against authentic standards of NBPT havinga nominal purity of >99%. FIG. 1 shows the results of the acceleratedstability testing.

This test shows that the NBPT did not have significant deterioration atelevated temperatures meaning that the formulations of the presentinvention can be transported without worrying about significantdegradation of the product.

Example 6

An NBPT solution was prepared by thoroughly mixing NBPT, DMSO, and PG toobtain the following percentages by weight: 35% PG, 40% DMSO, and 25%NBPT. The commercially available NBPT solution of example 2 was alsoused for comparison.

Example 7

The NBPT solutions of example 6 were placed into individual vials andincubated for 45 days at 50±1° C. in a laboratory oven. Samples wereperiodically removed and analyzed using the procedures of example 5.FIG. 2 shows the results of the accelerated stability testing.

This test shows that the NBPT did not have significant deterioration atelevated temperatures when the relative amounts of DMSO are varied.Accordingly, the formulations of the present invention can betransported without worrying about significant degradation of theproduct at different DMSO levels.

Example 8

An NBPT solution was prepared by thoroughly mixing NBPT, DMSO, and PG toobtain the following percentages by weight: 20% PG, 40% DMSO, and 40%NBPT. The commercially available NBPT solution of example 2 was alsoused for comparison.

Example 9

The NBPT solutions of example 8 were placed into individual vials andincubated for 45 days at 50±1° C. in a laboratory oven. Samples wereperiodically removed and analyzed using the procedures of example 5.FIG. 3 shows the results of the accelerated stability testing.

This test shows that the NBPT did not have significant deterioration atelevated temperatures when the relative amount of NBPT is increased.Accordingly, the formulations of the present invention can betransported without worrying about significant degradation of theproduct even at a relatively high NBPT concentration.

Example 10

An NBPT solution was prepared by thoroughly mixing NBPT, DMSO,glycerine, and methanol to obtain the following percentages by weight:48.5% glycerine, 1.5% methanol, 25% DMSO, and 25% NBPT. The commerciallyavailable NBPT solution of example 2 was also used for comparison.

Example 11

The NBPT solutions of example 10 were placed into individual vials andincubated for 45 days at 50±1° C. in a laboratory oven. Samples wereperiodically removed and analyzed using the procedures of example 5.FIG. 4 shows the results of the accelerated stability testing.

This test shows that the NBPT did not have significant deterioration atelevated temperatures with this formulation meaning that thisformulation can be transported without worrying about significantdegradation of the product.

Example 12

An NBPT solution was prepared by thoroughly mixing NBPT, DMSO,glycerine, and methanol to obtain the following percentages by weight:33.5% glycerine, 1.5% methanol, 25% DMSO, and 40% NBPT. The commerciallyavailable NBPT solution of example 2 was also used for comparison.

Example 13

The NBPT solutions of example 12 were placed into individual vials andincubated for 45 days at 50±1° C. in a laboratory oven. Samples wereperiodically removed and analyzed using the procedures of example 5.FIG. 5 shows the results of the accelerated stability testing.

This test shows that the NBPT did not have significant deterioration atelevated temperatures with this formulation meaning that thisformulation can be transported without worrying about significantdegradation of the product.

Example 14

A buffer solution was prepared by carefully mixing monoisopropanolamine(MIPA) with glacial acetic acid (GAA) to obtain the followingpercentages by weight: 62.5% MIPA, 37.5% GAA. The mixing was conductedsuch that the temperature of the mixture remained below 50° C. MultipleNBPT solutions were prepared to obtain the following percentages byweight:

Mix A: 75% N-methyl pyrrolidone, 25% NBPT; Mix B: 75% PG, 25% NBPT; MixC: 75% Buffer Solution, 25% NBPT; Mix D: 75% DMSO, 25% NBPT.

Example 15

The four NBPT solutions of example 14 were placed into individual vialsand incubated for approximately 200 hrs. at 50±1° C. Samples wereperiodically removed and analyzed using the HPLC procedures of example5. FIG. 6 shows the results of the accelerated stability testing.

This test shows that Mix C had more sample degradation at elevatedtemperatures than mixtures containing DMSO (Mix D), NMP (Mix A) or PG(Mix B). It should be noted that PG does not have the pourability ofDMSO and NMP is more toxic than DMSO.

Example 16

Dynamic viscosity measurements were collected for propylene glycol,glycerin, and a representative alkanolamine (monoisopropanolamine, MIPA)with increasing levels of DMSO and NMP. A Brookfield LVDV-E digitalrotational viscometer with LVDV-E spindle set (Brookfield EngineeringLabs, Inc., Middleboro, Mass.) was employed for this work and wascalibrated using Cannon N14 general purpose, synthetic base oilviscosity calibration standard solution (Cannon Instrument Company,State College, Pa.). The sampling was conducted at 21° C. FIGS. 7, 8,and 9 display the ability of DMSO to depress the viscosity of NBPTmixtures at 21° C. as a function of concentration, relative to similarNMP measurements.

This test shows that there is virtually no difference between DMSO andNMP in reducing the viscosity of various viscous formulations.

Example 17

A dye solution was added to the solution of example 1. 454 grams ofgranular urea was added to two clean, dry glass 2000 mL media bottles.Using a pipette, 1.87 mL, to represent application rate of 2 quartsproduct/ton urea of the dyed solution in example 1, was added to theurea in one of the bottles. Using a pipette, 1.87 mL, to representapplication rate of 2 quarts product/ton urea of the commercial solutionof example 2, was added to the urea in the other bottle. With the lidon, the media bottles were rotated hand over hand (1 rotation=360-degreehand over hand turn) until the urea was consistently coated. Morecomplete coverage was observed after four turns in the dyed solution ofexample 1. The number of rotations required to obtain 100% visualcoverage was recorded. The dyed solution of example 1 required 30rotations for complete coverage, while the commercial product of example2 required 35 rotations.

This test shows that formulations containing DMSO and a dye can moreeasily cover urea than a corresponding solution containing NMP and adye.

Example 18

The NBPT solutions of examples 4, 6, 8, 10, and 12, together with thecommercial NBPT solution of example 2, were placed in a −20° C. freezerfor 48 hrs. The NBPT solutions of examples 4, 6, 8, and the commercialNBPT solution of example 2, were all freely flowable at −20° C. The NBPTsolution of example 10 was very viscous but still flowable. The NBPTsolution of example 12 was a solid at −20° C.

Example 19

Commercial granulated urea was treated with the NBPT solution ofexample 1. Both untreated and treated urea were applied to acommercially available potting soil blend at 22° C., and ammoniaconcentrations in the headspace were measured for a 7-day period using achemiluminescence analyzer. Ammonia concentrations in the treated ureawere considerably less than those in the untreated urea. FIG. 10 showsthe results of the ammonia emissions testing.

This test shows that NBPT formulations containing DMSO are effective atreducing the hydrolysis of urea to ammonium, thereby reducing ammonialosses to the atmosphere and making the fertilizer more effective.

In certain embodiments, the present invention relates to formulations,fertilizer additives, methods and processes of making and using theseformulations and/or fertilizer additives.

In an embodiment, the present invention relates to a formulationcomprising N-(n-butyl) thiophosphoric triamide and one or more of anC₁₋₆alkylene carbonate and R₁S(O)xR₂ wherein R₁ and R₂ are eachindependently a C₁₋₆ alkylene group, an aryl group, or C₁₋₃alkylenearylgroup or R₁ and R₂ with the sulfur to which they are attached form a 4to 8 membered ring wherein R₁ and R₂ together are a C₁₋₆ alkylene groupwhich optionally contains one or more atoms selected from the groupconsisting of O, S, Se, Te, N, and P in the ring and x is 1 or 2. In avariation, the atoms in the ring may optionally include O, S, N and P oralternatively, O, S, and N.

In one embodiment, the formulation contains R₁S(O)xR₂, which is dimethylsulfoxide. Alternatively, the formulation contains R₁S(O)xR₂, which is adialkyl, diaryl, or alkylaryl sulfoxide. Alternatively, R₁ and R₂ may bethe same or different and each of R₁ and R₂ may be C₁₋₆ alkylene group,an aryl group, or C₁₋₃alkylenearyl group.

In an embodiment, R₁ is methyl, ethyl, n-propyl, phenyl or benzyl and R₂is methyl, ethyl, n-propyl, phenyl or benzyl or mixtures thereof. Inanother embodiment, R₁S(O)xR₂ is sulfolane.

In an embodiment, the formulation may contain akylene carbonate, whichis ethylene carbonate, propylene carbonate, butylene carbonate ormixtures thereof. In a variation, the formulation may contain akylenecarbonate, which is ethylene carbonate, propylene carbonate, or mixturesthereof.

In an embodiment, the formulation may further comprise an alcohol orpolyol wherein the polyol is alkylene or poly(alkylene) glycols ormixtures thereof. In an embodiment, the polyol is an alkylene glycolselected from the group consisting of ethylene, propylene, and butyleneglycol, or mixtures thereof. In an embodiment, the polyol is glycerin.

In an embodiment, the formulation may further comprise an alkanolamineselected from the group consisting of ethanolamine, diethanolamine,dipropanolamine, methyl diethanolamine, monoisopropanolamine andtriethanolamine.

The formulation(s) may contain an aqueous ethanolamine borate such asARBORITE Binder. In one embodiment, the concentration of the secondaryor tertiary amino alcohol may be kept above about 12% and alternatively,above about 20%. When the concentration of aqueous ethanolamine borateis below about a 12% concentration, a suspension of NBPT in the aqueousmixture may form which can be solved by agitation to be used to prepareother products.

In an embodiment of the invention, NBPT may be dissolved by melting thecompound with sufficient triethanolamine to provide a mixture with up toabout 30% by weight of NBPT. The resulting NBPT mixture intriethanolamine can be used to treat urea as described herein.

In another embodiment of the invention, NBPT is dissolved indiethanolamine in an amount up to 40% by weight by melting the solidinto diethanolamine until a solution is obtained. The NBPTdiethanolamine mixture may be used to treat urea as described herein.

In another embodiment of the invention, a liquid mixture ofdiisopropanolamine may be prepared by gently warming the solid until ithas liquefied and the mixing NBPT with the solid up to the solubilitylimit. The liquid NBPT containing mixture in disioproanolamine may beused to treat urea as described herein.

In a variation, the formulation may further comprise ethyl, propyl, orbutyl lactate.

In an embodiment, the N-(n-butyl)-thiophosphoric triamide (NBPT) may bepresent in an amount that is between about 5-75 wt. % of theformulation. In a variation, the formulation may contain between about10 and 75 wt. % NBPT, 10 and 50 wt. % DMSO, and 10 and 80 wt. % PG (polyglycol) or alkylene carbonate. In a variation, the formulation maycontain between about 10 and 60 wt. % NBPT, 10 and 40 wt. % DMSO, and 10and 60 wt. % PG or alkylene carbonate. In a variation, the formulationmay contain between about 10 and 50 wt. % NBPT, 10 and 50 wt. % DMSO,and 10 and 50 wt. % PG or alkylene carbonate. In a variation, theformulation may contain between about 10 and 40 wt. % NBPT, 10 and 40wt. % DMSO, and 10 and 50 wt. % PG or alkylene carbonate. In avariation, the formulation may contain between about 20 and 50 wt. %NBPT, 20 and 50 wt. % DMSO, and 10 and 50 wt. % PG or alkylenecarbonate. In a variation, the formulation may be diluted with water.

In an embodiment, the present invention relates to a fertilizer additivecomprising N-(n-butyl) thiophosphoric triamide and one or more of anC₁₋₆alkylene carbonate and R₁S(O)xR₂ wherein R₁ and R₂ are eachindependently a C₁₋₆ alkylene group, an aryl group, or C₁₋₃alkylenearylgroup or R₁ and R₂ with the sulfur to which they are attached form a 4to 8 membered ring wherein R₁ and R₂ together are a C₁₋₆ alkylene groupwhich optionally contains one or more atoms selected from the groupconsisting of O, S, Se, Te, N, and P in the ring and x is 1 or 2.

In an embodiment, the fertilizer additive may compriseN-(n-butyl)-thiophosphoric triamide and dimethyl sulfoxide. In avariation, the fertilizer may further comprise polyalkylene glycols. Ina variation, the polyalkylene glycols are selected from the groupconsisting of polymethylene glycols, polyethylene glycols, polypropyleneglycols, polybutylene glycols, and mixtures thereof.

In an embodiment, the fertilizer additive may be any of the embodimentsdiscussed above as it relates to the formulation.

In an embodiment, the present invention relates to a method of reducingthe volatility of urea fertilizers comprising adding a composition thatcomprises N-(n-butyl)-thiophosphoric triamide and one or more of anC₁₋₆alkylene carbonate and R₁S(O)xR₂ wherein R₁ and R₂ are eachindependently a C₁₋₆ alkylene group, an aryl group, or C₁₋₃alkylenearylgroup or R₁ and R₂ with the sulfur to which they are attached form a 4to 8 membered ring wherein R₁ and R₂ together are a C₁₋₆ alkylene groupwhich optionally contains one or more atoms selected from the groupconsisting of O, S, Se, Te, N, and P in the ring and x is 1 or 2.

In an embodiment, the present invention relates to a method of making aformulation and/or fertilizer additive, wherein toN-(n-butyl)-thiophosphoric triamide is added one or more of anC₁₋₆alkylene carbonate and R₁S(O)xR₂ wherein R₁ and R₂ are eachindependently a C₁₋₆ alkylene group, an aryl group, or C₁₋₃alkylenearylgroup or R₁ and R₂ with the sulfur to which they are attached form a 4to 8 membered ring wherein R₁ and R₂ together are a C₁₋₆ alkylene groupwhich optionally contains one or more atoms selected from the groupconsisting of O, S, Se, Te, N, and P in the ring and x is 1 or 2.

In an embodiment, the methods may comprise R₁S(O)xR₂, which is dimethylsulfoxide.

In an embodiment, the methods may comprise C₁₋₆alkylene carbonate, whichis ethylene carbonate, propylene carbonate, butylene carbonate ormixtures thereof.

In an embodiment, the methods may comprise any of the formulationsand/or fertilizer additives discussed above.

Every patent mentioned herein is incorporated by reference in itsentirety.

It should be understood that the present invention is not to be limitedby the above description. Modifications can be made to the above withoutdeparting from the spirit and scope of the invention. It is contemplatedand therefore within the scope of the present invention that any featurethat is described above can be combined with any other feature that isdescribed above. Moreover, it should be understood that the presentinvention contemplates minor modifications that can be made to theformulations, compositions, fertilizer additives and methods of thepresent invention. When ranges are discussed, any number that may not beexplicitly disclosed but fits within the range is contemplated as anendpoint for the range. The scope of protection to be afforded is to bedetermined by the claims which follow and the breadth of interpretationwhich the law allows.

What is claimed is:
 1. A composition comprising: a. a nitrogenfertilizer comprised of urea and one or more members selected from thegroup consisting of a) urea formaldehyde polymer and b) dicyandiamide,b. a liquid solution comprised of a urease inhibitor that has beensolubilized within an aprotic solvent wherein said aprotic solventcomprises dimethyl sulfoxide, wherein the composition comprises 45-5% ofsaid urease inhibitor and 55-95% of dimethyl sulfoxide and wherein saidurease inhibitor is N-(n-butyl) thiophosphoric triamide.
 2. Thecomposition of claim 1, wherein the composition further comprisesaprotic solvents and protic solvents, wherein said aprotic solvents areone or more members selected from the group consisting of a) one or morealkylene carbonates selected from the group consisting of propylenecarbonate, ethylene carbonate, and butylene carbonate, b) 2-methoxyethylether, c) cyclohexylpyrrolidone, d) 1,3 dimethyl-2-imidazolidinone e)dimethyloxyethane, and f) organo phosphorous liquid hexamethylphosphoramides, and wherein said protic solvents are one or more membersselected from the group consisting of a) glycerine, b) ethyl lactate andc) one or more alcohols selected from the group consisting of n-propylalcohol, isopropyl alcohol, cyclohexanol, isobutyl alcohol, andtert-amyl alcohol.
 3. The composition of claim 1, wherein thecomposition further comprises one or more members selected from thegroup consisting of buffer, flow aids, silicas, surfactants anddyes/colorants.
 4. The composition of claim 1, wherein the compositionfurther comprises water thereby resulting in a liquid urea fertilizer.5. The composition of claim 1, wherein said nitrogen fertilizer iscombined with said liquid solution to make fertilizer more effectivewhen applied to the soil for plant growth, wherein the compositionreduces hydrolysis of urea to ammonia, thereby reducing ammonia lossesto an atmosphere resulting in improved nitrogen retention in soil.
 6. Acomposition comprising: a. a nitrogen fertilizer comprised of urea andone or more members selected from the group consisting of a) ureaformaldehyde polymer and b) dicyandiamide, b. a liquid fertilizeradditive comprised of urease inhibitor(s) that have been solubilizedwithin polar aprotic solvents and one or more solvents selected from thegroup consisting of aprotic and protic solvents wherein said polaraprotic solvents comprise one or more members selected from the groupconsisting of: i. dimethyl sulfoxide, and ii. one or more sulfoxide(s)selected from the group consisting of dialkyl, diaryl, or alkylarylsulfoxide(s) selected from the formula structure:R⁹S(O)_(x)R¹⁰ wherein
 1. R⁹ and R¹⁰ are each independently a C₁-C₆alkylene group, an aryl group, or C₁-C₃ alkylenearyl group,
 2. or R⁹ andR¹⁰ with the sulfur to which they are attached form a 4 to 8 memberedring wherein R⁹ and R¹⁰ together are a C₁-C₆ alkylene group whichoptionally contains one or more atoms selected from the group consistingof O, S, Se, Te, N, and P in the ring,
 3. x=1 or 2, wherein thecomposition comprises 75-5% of said urease inhibitors and 25-95% of saidpolar aprotic, said aprotic, and said protic solvents.
 7. Thecomposition of claim 6, wherein the composition comprises one or moreurease inhibitors selected from the group consisting of an aliphaticphosphoric triamide, phosphoramides, and N-alkyl thiophosphorictriamides.
 8. The composition of claim 6, wherein the compositioncomprises the urease inhibitor N-(n-butyl) thiophosphoric triamide. 9.The composition of claim 6, wherein the composition comprises the polaraprotic solvent dimethyl sulfoxide.
 10. The composition of claim 6,wherein the composition comprises one or more aprotic solvents selectedfrom the group consisting of: a) one or more alkylene carbonatesselected from the group consisting of propylene carbonate, ethylenecarbonate, and butylene carbonate, b) 2-methoxyethyl ether, c)cyclohexylpyrrolidone, d) 1,3 dimethyl-2-imidazolidinone, and e) organophosphorous liquid hexamethyl phosphoramides.
 11. The composition ofclaim 6, wherein the composition comprises one or more protic solventsselected from the group consisting of a) one or more C₁ to C₆ alcohols,b) one or more polyols selected from the group consisting of alkyleneand poly(alkylene) glycols, glycerin, c) one or more alkanolaminesselected from the group consisting of ethanolamine, diethanolamine,dipropanolamine, methyl diethanolamine, monoisopropanolamine, andtriethanolamine, and d) one or more alkyl lactates selected from thegroup consisting of ethyl, propyl and butyl lactate.
 12. The compositionof claim 6, wherein the composition comprises one or more polyalkyleneglycols selected from the group consisting of: polymethylene glycol,polyethylene glycol, polypropylene glycol, and polybutylene glycol. 13.The composition of claim 6, wherein the composition comprises one ormore alkylene glycols selected from the group consisting of ethyleneglycol, propylene glycol, and butylene glycol.
 14. The composition ofclaim 6, wherein the composition further comprises one or more membersselected from the group consisting of buffers, flow aids, silicas,surfactants, and dyes/colorants.
 15. The composition of claim 6, whereinthe composition further comprises water thereby resulting in a liquidurea fertilizer.
 16. The composition of claim 1, wherein the saidnitrogen fertilizer is combined with said fertilizer additive to makefertilizer more effective when applied to the soil for plant growth,wherein the fertilizer additive reduces the hydrolysis of urea toammonia, thereby reducing ammonia losses to an atmosphere improvingnitrogen retention in soil.
 17. The composition of claim 6, wherein thecomposition comprises 2 quarts of the liquid fertilizer additive per tonof urea.
 18. A composition comprising: a. a nitrogen fertilizercomprised of urea and one or more members selected from the groupconsisting of a) urea formaldehyde polymer and b) dicyandiamide, b. aliquid solution comprised of a urease inhibitor that has beensolubilized within an aprotic solvent wherein said aprotic solventcomprises dimethyl sulfoxide, wherein the composition comprises 58.9-5%of said urease inhibitor and wherein said urease inhibitor isN-(n-butyl) thiophosphoric triamide.
 19. The composition of claim 18,wherein the composition further comprises one or more members selectedfrom the group consisting of buffer, flow aids, silicas, surfactants anddyes/colorants.